持续静脉泵注利多卡因对脓毒症大鼠肺组织高迁移率族蛋白B1基因表达的影响

The effect of continuous infusion of lidocaine on high mobility group box 1 expression in lung tissue of sepsis model rats

目的探讨不同时期持续静脉输注利多卡因对脓毒症大鼠肺组织中高迁移率族蛋白B1(high mobility group box 1,hMGB1)基因表达的影响及机制。方法将75只健康雄性SD大鼠按随机数字表法分成5组(每组15只):假手术组(S组)、盲肠结扎穿孔(cecal ligation and puncture, CLP)组、CLP前3h输注利多卡因组(L1组)、CLP即刻输注利多卡因组(L2组)以及CLP后3h输注利多卡因组(L3组)。 S组打开腹腔后缝合,其他各组采用CLP制备脓毒症模型,L1组、L2组和L3组分别在CLP前3h、CLP即刻以及CLP完成3h后予以持续输注利多卡因3h,S组和CLP组予以等量生理盐水代替。于CLP后24h处死大鼠,ELISA法检测血清中IL-6、TNF-α以及HMGB1浓度,实时荧光定量PCR法检测肺组织中HMGB1 mRNA的表达量。全自动生化分析法检测血清ALT、AST、Cr。另取50只大鼠分组同上观察72h生存情况。结果与S组比较,CLP组、L1组、L2组、L3组均发生脓毒症,且血清IL-6、TNF-α、HMGB1浓度和肺组织中HMGB1 mRNA表达量均增高(P<0.05)。 L1组、L2组、L3组血清中HMGB1、IL-6、TNF-α以及肺组织中HMGB1 mRNA较CLP组均明显降低(P<0.05)。与S组比较,CLP组、L1组L2组和L3组ALT、AST、Cr均有升高(P<0.05),与CLP组比较,L1、L2、L3组ALT、AST、Cr均有降低(P<0.05)。与CLP组比较,L1、L2、L3组生存率明显提高。结论脓毒症可以使大鼠促炎因子表达增强,持续静脉泵注利多卡因可以有效降低脓毒症大鼠炎症因子IL-6、TNF-α,HMGB1的表达,抑制肺组织中HMGB1基因表达量,减轻脓毒症对肺的损伤,有效提高动物存活率。

Objective To evaluate the effect and mechanism of intravenous infusion of lidocaine on the expression of high mobility group box 1 (HMGB1) mRNA in lung of sepsis model rats. Methods Senenty-five healthy male Sprague-Dawley (SD) rats were stochastically divided into 5 groups (n=15): S group (group S), cecal ligation and puncture (CLP) group (group CLP), pre-CLP infusion the lidocaine group (group L1), CLP immediately infused with lidocaine (group L2) and CLP infused with the lidocaine-treated group (group L3). Group S suture abdominal cavity after opening it while other groups were ligated with cecal ligation and puncture. groups L1, L2 and L3 were infused with lidocaine for 3 h before CLP, at the moment of CLP started and 3 h after CLP was completed respectively. The group S and the group CLP were replaced by the same amount of normal saline. The rats were sacrificed 24 h after the CLP model was successfully established. The serum levels of pro-inflammatory cytokines IL-6, TNF-α and HMGB1 concentration were measured by enzyme-limked immunosorbent assay(ELISA). The expression of HMGB1 mRNA in lung tissue was detected by qRT-PCR. Automated biochemical analysis was used to detect serum ALT, AST, and Cr. Another 50 rats were grouped and observed for 72 h. Results Compared with group S, CLP occurred in the group CLP, group L1, group L2 and group L3, IL-6, TNF-α, HMGB1 concentrations and the expression of HMGB1 mRNA were increased in lung tissues (P<0.05). The serum levels of HMGB1, IL-6, TNF-α and HMGB1 mRNA in lung tissues of the groups L1, L2 and L3 were significantly lower than those in the group CLP (P<0.05). Compared with group S, ALT, AST and Cr were increased in groups CLP, L1, L2, and L3(P<0.05). Compared with group CLP, ALT, AST and Cr were decreased in groups L1, L2 and L3(P<0.05). Compared with the group CLP, the survival rates of the groups L1, L2 and L3 were significantly improved. Conclusions CLP can increase the expression levels of pro-inflammatory cytokines in rats. Intravenous infusion of lidocaine can effectively reduce the expression of inflammatory factors in CLP rats and inhibit the expression of HMGB1 mRNA in lung tissues. Thus, it reduces the lung damage caused by CLP and improves the survival rate effectively.